Protective effect of Anwulignan against D-galactose-induced hepatic injury through activating p38 MAPK–Nrf2–HO-1 pathway in mice

Background: Liver aging is a significant risk factor for chronic liver diseases. Oxidative stress has been considered as a conjoint pathological mechanism for the initiation and progression of liver aging. It has been reported that d-galactose (d-gal)-induced hepatic injury is an experimental model well established closely similar to morphological and functional features of liver aging. Schisandra sphenanthera Rehd. et Wils (S. sphenanthera, Schisandraceae), as a famous tradi-tional Chinese medicine, has been used for thousands of years in China to treat various disorders, including liver dysfunctions. This study was aimed to understand whether Anwulignan, one of the monomeric compounds in the lignans from S. sphenanthera, could improve the hepatic injury induced by d-gal in mice and to examine the possible mechanisms. Methods: ICR mice were used to produce hepatic injury by 220 mg kg-1 d-gal subcutaneously once daily for 42 days. The effects of oral Anwulignan on liver index; serial AST and ALT levels; histological changes; SOD, GSH-Px, MDA, and 8-OHdG in the liver and peripheral blood; expression of p38 mitogen-activated protein kinase (MAPK), Nrf2, and HO-1 in the liver; and HepG2 cell viability, and decrease caspase-3 contents in liver were examined. Results: Anwulignan could significantly increase the liver index, lower aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in the peripheral blood, elevate superoxide dis-mutase (SOD) and glutathione peroxidase (GSH-Px) activities, and decrease malonaldehyde (MDA) and 8-hydroxy-2-deoxyguanosine (8-OHdG) contents in the peripheral blood and liver. Furthermore, Anwulignan could upregulate the expression of p38 mitogen-activated protein kinase (MAPK), Nrf2, and HO-1 in the liver, increase the HepG2 cell viability, and decrease caspase-3 contents in liver. Conclusion: Anwulignan has protective effects against the hepatic injury induced by d-gal, which may be related to its antioxidant capacity through activating p38 MAPK-Nrf2-HO-1 pathway, increases the injured cell viability, and decreases the caspase-3 contents in liver.